San Diego, CA /PRNewswire/ - Wellspring Biosciences, Inc., a wholly owned subsidiary of Araxes Pharma, LLC, announced today that the U.S. Food and Drug Administration has cleared an investigational new drug (IND) application for ARS-3248, a small molecule KRAS G12C inhibitor. ARS-3248 was discovered as part of an exclusive drug discovery and development agreement with Janssen Biotech, Inc, which will conduct the Phase 1 trial and have sole responsibility for clinical development.
"Although KRAS was considered an undruggable target when we initiated this program in 2012, Wellspring scientists have shown considerable progress in being the first to demonstrate that direct and covalent inhibitors can specifically induce tumor regression in mouse tumor models harboring the mutation," said Yi Liu, Ph.D., Chief Scientific Officer of Wellspring Biosciences. "ARS-3248 represents the culmination of a significant and highly productive collaboration between scientists at Wellspring and Janssen, building upon the learnings of previous tool compounds. As we continue to advance this optimized clinical candidate that holds the potential to provide meaningful benefit to patients, we look forward to supporting Janssen as they evaluate the potential of ARS-3248 in patients with KRAS G12C-positive cancers."
ARS-3248 is an investigational, orally available small molecule that is designed to potently and selectively inhibit a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 12 percent of non-small cell lung cancer patients, as well as subsets of patients in other tumor types, such as those with colorectal and pancreatic cancers. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. ARS-3248 will be evaluated in a Phase 1 trial of patients with molecularly identified KRAS G12C-positive advanced solid tumors.
About Wellspring Biosciences
Wellspring and its parent company, Araxes Pharma, are closely held and committed to creating breakthrough medicines for the treatment of cancer and other serious diseases. The companies were founded by Yi Liu, Ph.D., Pingda Ren, Ph.D., Kevan Shokat, Ph.D. and Troy Wilson, Ph.D., J.D., based upon pioneering research into KRAS G12C inhibitors conducted by Dr. Shokat, HHMI Investigator and Professor of Molecular and Cellular Pharmacology, and colleagues at the University of California, San Francisco. The Shokat group discovered a novel, small molecule approach to bind G12C mutant K-Ras and inhibit SOS-catalyzed K-Ras activation1. Building upon those pioneering efforts, Wellspring discovered ARS-853, a cell-active, mutant-specific, covalent inhibitor of KRAS G12C that targets the GDP-bound, inactive state and prevents subsequent activation of KRAS2. Wellspring discovered ARS-1620, the first small molecule inhibitor that induced tumor regression in patient-derived tumor models that served as a valuable pharmacologic tool to interrogate KRAS biology in vivo3. Wellspring, through Araxes Pharma, entered into an exclusive arrangement with Janssen in February 2013 to develop small molecule inhibitors of the KRAS G12C oncoprotein for the treatment of cancer. Scientists at both Wellspring and Janssen have made significant contributions in the discovery and development of potent, selective KRAS G12C inhibitors.
1 J. M. Ostrem et al., Nature 2013; 503(7477): 548–551
2 M.P. Patricelli et al., Cancer Discovery 2016; 6(3); 316–29
3 M.R. Janes et al., Cell 2018, 172(3); 578-589
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